Cardiac tropism radiopharmaceutical products incorporating a nitride complex of a transition metal and having a rapid myocardial clearance

ABSTRACT

The present invention relates to cardiac tropism radiopharmaceutical products incorporating a nitride complex os a transition metal and having a rapid myocardial clearance. 
     These complexes are based on the formula: 
     
         (M.tbd.N)L.sup.1 L.sup.2                                   (I) 
    
     in which M is a transition metal such as  99m  Tc and L 1  and L 2  comply with the formula: ##STR1## in which at least one of the R and R&#39; represents a branched alkyl group having one or more ether functions, a tetrahydrofurfuryl or ether group, a tetrahydrofurfuryl or dioxaspiro or dialkoxy piperidino groups.

This application is a 371 of PCT/FR96/01103, filed Jul. 16, 1996.

BACKGROUND OF THE INVENTION

The present invention relates to a cardiac tropism radiopharmaceuticalproduct incorporating a nitride complex of a transition metal M having acentral part M.tbd.N usable for myocardial scintigraphy.

According to the invention, the term transition metal is understood tomean a metal, whose layer d is partly filled in the usual degree ofoxidation of said metal. It applies to elements of periods III to XII ofthe periodic table of elements having eighteen columns. Examples of suchmetals are Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nband Ta.

Technetium nitride complexes have been described by J. Baldas et al. inthe following documents: international patent application WO-85/03063,J. Chem. Soc. Dalton Trans., 1981, pp 1796-1801 and the book "Technetiumin Chemistry and Nuclear Medicine", Ed. M. Nicolini, G. Bandoli, U.Mazzi, Cortine Int. Verone, 1986, pp 103 to 108.

DESCRIPTION OF THE BACKGROUND

Technetium nitride complexes having a cardiac tropism have beendescribed in WO-A-90/06137. These complexes have a central portionM.tbd.N and ligands of the dithiocarbamate type having side groups ofthe alkyl type, optionally substituted by alkoxy, alkylcarboxy,carbamoyl or amino groups.

These complexes have good biological properties with respect to theircardiac retention, but can have a disturbing, early pulmonary fixationfor myocardial examinations and they are relatively slowly eliminatedfrom the organism, particularly the heart.

This is a disadvantage for the scintigraphic examination of themyocardiuim. Thus, a complete examination of the myocardium generallyrequires two injections of the radiopharmaceutical product, one at restand the other after an effort test. With radiopharmaceutical productshaving a stable fixation in the myocardium, these four injections mustbe spaced by a minimum of 4 hours in order to eliminate the residualcardiac activity due to the first injection. It would therefore be ofsignificant interest to have more rapidly eliminated, cardiac tropismradiopharmaceutical products.

Another problem encountered with radiopharmaceutical products of thistype is their hepatic fixation, which can be prejudicial if it is of apersistent nature. Thus, such a fixation does not make it possible tocarry out a satisfactory scintigraphic examination of the myocardium,when the second injection is too close to the first. It would thereforebe of interest to have cardiac tropism radiopharmaceutical productswhich are rapidly eliminated from the liver and heart.

SUMMARY OF THE INVENTION

The present invention relates to radiopharmaceutical productsincorporating a transition metal nitride complex, which are more rapidlyeliminated from the heart and which do not have disturbing pulmonary andhepatic fixations. These complexes also comprise ligands of thedithiocarbamate type, but the alkyl groups of these ligands are either abranched chain having at least one ether function, or a branched chain,whereof a carbon atom is substituted by two alkoxy groups, whichcorresponds to an acetyl function.

According to the invention, the radiopharmaceutial product comprises acomplex of a transition metal complying with the formula:

    (M.tbd.N)L.sup.1 L.sup.2                                   (I)

in which M is a transition metal, and L¹ and L², which can be the sameor different, comply with the formula: ##STR2## in which R and R', whichare the same or different, represent: an alkyl group,

a group of formula: ##STR3## in which:

R¹ is an alkyl group, R² is an alkyl group or an alkoxy group, or R¹ andR² form together the group --CH₂ CH₂ O--,

R¹ is an alkyl group, R² is an alkyl group or an alkoxy group, or R¹ andR² form together the group --CH₂ CH₂ O--,

R³ is a hydrogen atom or an alkyl group and n is equal to 0, 1, 2 or 3,

a group of formula: ##STR4## in which R¹ and R³ are as definedhereinbefore and R⁴ is an alkyl group,

the group of formula: ##STR5## a group of formula:

    R.sup.1 O(CH.sub.2 CH.sub.2 O).sub.p CH.sub.2 CH.sub.2 --  (VI)

in which R¹ is as defined hereinbefore and p is equal to 1 or 2, or inwhich R and R' together with the nitrogen atom to which they are linked,form the group of formula: ##STR6## in which R¹ and R⁵ are identical ordifferent alkyl groups, or in which R¹ and R⁵ form together --CH₂ --CH₂--, provided that both R and R' do not represent an alkyl group.

DETAILED DESCRIPTION OF THE INVENTION

The ligands L¹ and L² of the transition metal complex according to theinvention thus incorporate a branched alkyl group of formula (III) orformula (V), a tetrahydrofurfuryl group, a straight polyether-typegroup, or a dioxaspiro or dialkoxy piperdino-type group, which givesthem better clearance properties.

In the complexes of the invention, the transition metal M is inparticular chosen as a function of the application of theradiopharmaceutical product.

Thus, when it is wished to use the product for diagnosis, use is made ofa radioactive transition metal having a relatively short period. e.g.technetium^(99m).

In the case where it is wished to use the radiopharmaceutical productfor therapy, use is made of a transition metal emitting an effectiveradiation for the therapy and having a longer life, such as rhenium,e.g. Re-186 or Re-188.

In the formula given hereinbefore for R and R', the alkyl groupsrepresented by R¹, R², R³, R⁴ and R⁵ can be straight or branched. Ingeneral, use is made of alkyl groups having 1 to 5 carbon atoms,particularly ethyl and methyl groups.

The alkyl group used for R or R' can also be straight or branched andpreferably have 1 to 5 carbon atoms.

When R² represents an alkyl group, it can also be a straight or branchedgroup and preferably said alkoxy group has 1 to 5 carbon atoms.

In the transition metal complex according to the invention, the ligandsL¹ and L² can be the same or different and are preferably the same.

According to a first embodiment of the invention, at least one of the L¹and L² complies with the formula (II) in which:

R and/or R' represent an acetal group of formula: ##STR7## in which R¹represents an alkyl group, e.g. the ethyl or methyl group, R² representsan alkoxy group, e.g. the ethoxy or methoxy group, R¹ represents ahydrogen atom or an alkyl group, e.g. the methyl group, and n is equalto 0, 1, 2 or 3.

According to a second embodiment of the invention, at least one of theligands L¹ and L² complies with formula (II) in which R and/or R'represent a group of formula: ##STR8## in which R¹, R² and R³ areidentical or different alkyl groups, e.g. the methyl group.

According to a third embodiment of the invention, at least one of theligands L¹ and L² complies with the formula (II) in which:

R and/or R' comply with the formula (IV): ##STR9## in which R¹represents an alkyl group, e.g. the methyl group, R³ represents ahydrogen atom and R⁴ represents an alkyl group, such as the ethyl ormethyl group.

According to a fourth embodiment of the invention, at least one of theL¹ and L² complies with the formula (II) in which:

R and/or R' represent the group of formula: ##STR10##

The technetium nitride complexes used in the invention can be preparedby conventional processes, e.g. by the Baldas process. However, they arepreferably prepared by simpler processes, which can be more easilycarried out in a hospital and which lead to high yields, e.g. theprocesses described in WO-A-93/01839, WO-A-92/00982 and WO-A-90/6137.

Preferably, according to the invention use is made of the processdescribed in W092/00982 consisting of reacting in solution an oxygencompound of the transition metal M, with

1) a nitrogen ligand constituted either by a pharmaceutically acceptablemetal or ammonium nitride, or by a nitrogen compound having a N--N unit,in which the N's are connected to hydrogen atoms and/or monovalentorganic groups, e.g. via a carbon atom or a S atom, or in which one ofthe N's is connected to the carbon atom of a divalent organic group viaa double bond and the other N is connected to hydrogen atoms and/ormonovalent organic groups, e.g. via a carbon atom;

2) a reducing agent constituted either by a pharmaceutically acceptablemetal or ammonium dithionite, or by the tin II present in ionic form inthe solution; and

3) a compound complying with the formula: ##STR11## in which R and R'have the meanings given hereinbefore, R⁶ is an alkali metal ion, H⁺ andNH⁴⁺, and x is equal to 0 or an integer from 1 to 5.

This reaction between the oxygen compound of the transition metal, thereducing agent, the nitrogen ligand and the compound of formula (VIII)can be performed in one or two stages.

Working preferably takes place in two stages. Thus, in a first stage theoxygen compound of the transition metal is reacted with the nitrogenligand and the reducing agent, and in a second stage the productobtained at the end of the first stage is reacted with the compound offormula (VIII).

When tin (II) is used as the reducing agent, it can be introduced intothe solution from one or more reagents able to keep it in ionic form inthe presence of the nitrogen ligand and the compound of formula (VIII).

The tin can in particular be introduced in the form of the tin (II)salt, e.g. stannous chloride dihydrate. In order to keep it in ionicform in the solution, simultaneous addition takes place of a complexingagent having a complexing power with respect to the tin which isstronger than those of the nitrogen ligand and the compound of formula(VIII). The complexing agent can in particular be1,2-diamino-propane-N,N,N',N'-tetraacetic acid or a salt thereof.

Preferably, according to the invention, stannous chloride dihydrate isused as the reducing agent and succinyl dihydrazide as the nitrogenligand.

The compounds of formula (VIII) used for the preparation of theradio-pharmaceutical products according to the invention can be preparedby conventional processes from the corresponding amines of formula:##STR12## in which R and R' are as defined hereinbefore, by reactingthese amines with carbon disulphide in the presence of soda.

The secondary amines of formula (IX) can be prepared by reacting aprimary amine of formula:

    R--NH.sub.2

with a halogen of formula R'X, in which X is a halogen, preferably Br.

The radiopharmaceutical product according to the invention is generallyprepared at the time of use. The invention also relates to a kit for thepreparation of a cardiac tropism radiopharmaceutical product comprising:

a first bottle containing a tin salt and a complexing agent able tomaintain the tin in ionic form,

a second bottle containing the nitrogen ligand and

a third bottle containing a compound complying with formula (VIII).

According to a variant, the kit only has two bottles:

a first bottle containing the tin salt, the complexing agent for keepingthe tin in ionic form and the nitrogen ligand and

a second bottle containing the compound of formula (VIII).

Advantageously, the compound of formula (VIII) is chosen from among

sodium-(N-ethyl, N-(R,S)-2-methoxyisopropyl) dithiocarbamate,

sodium-(N-ethyl, N-(R)-2-methoxyisopropyl)-dithiocarbamate,

sodium-(N-ethyl, N-(S)-2-methoxyisopropyl)-dithiocarbamate,

sodium-[N,N-bis(2,2-dimethoxyethyl)]-dithiocarbaniate,

sodium-[N-(2,2-dimethoxyethyl),N-(3,3-dimethoxypropyl)]-dithiocarbamate,

sodium-[N-(2,2-dimethoxyethyl), N-ethyl)]-dithiocarbamate.

The products present in each bottle can be in the form of a solution orin lyophiliazed form.

With this kit, it is possible to directly prepare the desiredradio-pharmaceutical product in a nuclear medicine hospital department,by adding to the content of the first bottle a solution of the oxygencompound of the transition metal, e.g. an ammonium or alkali metalpertechnetate solution, then by adding to the thus obtained product thecontent of the second bottle.

In view of the fact that the products are intended for an intravenousinjection to living beings, appropriate production and preparationconditions must be used in order to obtain appropriately sterile andapyrogenic solutions.

In order to prepare the solutions, it is possible to use sterile,apyrogenic water or sterile, apyrogenic, alcoholic or hydroalcoholicsolutions, and carry out a storage of the solutions under nitrogen.

For preparing lyophilized compositions, solutions obtained under thesame conditions as hereinbefore are lyophilized in conventionalequipment.

The radiopharmaceutical products according to the invention can inparticular be used for scintigraphy of the myocardium.

In this case, following the preparation of the technetium nitridecomplex, the latter is injected into the patient to be examined, whichis followed by a scintigraphic examination of the heart.

For the injection of the product, the quantities of the differentligands are such that they substantially correspond to the stoichiometryof the complexes to be obtained. The final quantity injected moreparticularly depends on the ligands used and their toxicity. In general,satisfactory results are obtained by using total ligand quantitiesranging from 0.05 to 0.40 mg/kg of body weight.

The total dose of transition metal, e.g. technetium, is generally in therange 185 to 740 Mbq (5 to 20 millicuries).

With the administration of the transition metal nitride complex, it ispossible to carry out a satisfactory examination in a very short time,e.g. 2 to 5 minutes after the injection and a good contrast, clearimages and a good detection of lesions are obtained.

Moreover, with these compounds it is possible to carry out twosuccessive examinations in a very brief period, e.g. performing thesecond injection one hour after the first, due to the rapid clearance ofthe radiopharmaceutical products.

Thus, the radiopharmaceutical products according to the invention,particularly those in which the ligands have a branched R or R' groupwith an alkoxy substituent complying to formula (III), with R² and R³being alkyl groups and with R² being an alkoxy group and R³ a hydrogenatom, have the advantage of being eliminated from the liver by the gallduct and of thus concentrating the residual activity in the gallbladder. Thus, even when the second injection takes place one hour afterthe first, no disturbance is caused by the residual hepatic activity dueto the first injection, because said residual activity is in the gallbladder, namely in an area which does not interfere with the heartexamination.

The situation would not be the same on using radiopharmaceuticalproducts like those of the prior art, in which the ligands have a groupR of the straight alkoxy or alkoxyalkyl type, like the compounds ofexamples 11 and 17 of the aforementioned WO-A-90/06137.

Thus, in the case of these compounds where the R groups of the ligandsL¹ and L² respectively correspond to the formulas: ##STR13##

The residual hepatic fixation relates to all the liver one hour afterthe injection, because there is no activity concentration in the gallbladder.

Other features and advantages of the invention can be better gatheredfrom studying the following examples given in an illustrative andnon-limitative manner.

EXAMPLE 1

Preparation of thenitride-bis[N-ethyl,N-(R,S,2-methoxyisopropyl)-dithiocarbamate]^(99m)Tc(V) complex

1) Preparation of thesodium-(N-ethyl,N-(R,S)-2-methoxyisopropyl)dithiocarbamate.

a) Preparation of the (N-ethyl,N-(R,S)-2-methoxyisopropyl)-amine.

0.1 mole of (R,S)-2-methoxyisopropyl-amine (Aldrich) is dissolved in 100ml of water containing 0.2 mole of NaOH. In dropwise manner 0.1 mole ofbromethane is added. The solution is refluxed for one night. The aqueousphase is extracted by 200 ml of diethyl ether. The organic phase iswashed three times with 20 ml of 1N NaOH in water, in order eliminatethe primary amine which has not reacted. The organic phase is dried onsodium sulphate and the secondary amine is distilled TE_(b) =121° C.under 760 mm Hg.

b) Preparation ofsodium-(N-ethyl,N-(R,S)-2-methoxyisopropyl)dithiocarbamate

0.05 mole of the amine prepared in a) is dissolved in 200 ml of ethercontaining 0.1 mole of NaOH in pellet form. Dropwise addition takesplace of 0.1 mole of CS₂ and reaction is allowed to take place for 4hours at ambient temperature. The organic phase is filtered and 500 mlof n-heptane are added. It is allowed to recrystallize for one night at4° C., giving a white solid (sodium dithiocarbanate given as titer),which is recrystallized in an ether-n-heptane mixture.

NMR analysis in deuterium dimethyl sulphoxide (DMSO-D6).: ##STR14##

CH₃ O: singlet 3.35 ppm

CH₃ O--CH₂ : doublet 4.05 ppm

--CH: quintuplet 6.3 ppm

CH₃ --CH: doublet 0.9 ppm

CH₃ --CH₂ --N: triplet 1.1 ppm

CH₃ --CH₂ --N quadruplet 3.65 ppm.

2) Preparation of the intermediate (Tc.tbd.N)²⁺

Addition takes place of 0.5 to 5 ml of a sodium pertechnetate solution(^(99m) TcO₄ ⁻), 37 KBQ to 3.7 GBQ, to a penicillin-type bottlecontaining in lyophilized form:

20 μg of SnCl₂, 2H₂ O (stannous chloride dihydrate),

10 mg of succinyl dihydrazide (SDH),

5 mg of 1,2-diaminopropane-N-N,N',N'-tetraacetic acid,

10 mg of γ-cyclodextrin.

0.05 mmole of phosphate buffer at pH=7.80.

The reaction is allowed to carry on for 10 minutes at ambienttemperature, giving the intermediate (Tc.tbd.N)²⁺

3) Preparation of the final complex

Addition takes place of 1 ml of a sodium-(N-ethyl,N-(R,S)-2-methoxyisopropyl)-dithiocarbamate solution, as prepared in 1),to 10 mg/ml in water to the bottle containing the intermediate(Tc.tbd.N)²⁺. Reaction takes place for 5 minutes at ambient temperatureand the final complex is obtained.

Radiochemical purity is tested by carrying out reverse phase, thin filmchromatography (Whatman KC16F, eluent 30% methanol, 30% acetonitrile,20% THF, 0.5 M AcNH₄ in 20% H₂ O). The radiopharmaceutical obtained hasa Rf=0.52. The radiochemical purity is equal to or higher than 96%.

EXAMPLE 2

Preparation of the nitride-bis [(N-ethylNe(R)-2-methoxyisopropyl)-dithiocarbamate]^(99m) Tc(V) complex

1) Synthesis of the ligand sodium-(N-ethyl,N-(R)-2-methoxyisopropyl)dithiocarbamate

Firstly, the R-1-methoxyisopropyl amine is prepared in the followingway.

0.2 mole of R-2-amino-1-propanol (Aldrich) is dissolved in 200 ml ofanhydrous ether under a nitrogen atmosphere. Addition takes place of0.25 mole of metallic sodium (Na). Refluxing takes place for 6 hours.This is followed by the dropwise addition of 0.2 mole of methyl iodide.The solution is filtered, the filtrate dried on sodium sulphate and theamine is distilled, TE_(b) =93° C. at atmospheric pressure.

This is followed by the preparation of the substituted amine and thenthe corresponding sodium dithiocarbamate following the same operatingprocedure as in example 1, stages 1a) and 1b).

This gives the ligand sodium-N-ethyl,N-(2(R)-methoxyisopropyl)-dithiocarbamate. NMR analysis of this productin DMSO leads to a spectrum identical to that obtained in example 1.

2) Preparation of the intermediate (Tc.tbd.N)²⁺

The latter is prepared following the same operating procedure as inexample 1, but using sodium dithiocarbamate prepared in the precedingstage.

3) Preparation of the final complex

The latter is prepared as in example 1 from the previously obtainedintermediate. It has the following characteristics:

Rf=0.52

radiochemical purity≧97%.

EXAMPLES 3 TO 6

The same operating procedure as in examples 1 and 2 is followed forpreparing the technetium complexes given in table 1, the characteristicsof these complexes also being given in table 1.

EXAMPLE 7

Preparation of the nitride-bis-[N-ethyl,N-(R,S)-2-methoxypropyl)-dithiocarbamate]^(99m) Tc(V) complex.

Preparation firstly takes place of the ligand sodium-N-ethyl,N-(R,S-2-methoxypropyl)-dithiocarbamate working in the following way.

a) Preparation of R,S-2-methoxypropyl amine

0.2 mole of (R,S)-1-amino-2-propanol (Aldrich) is dissolved in 200 ml ofanhydrous ether under a nitrogen atmosphere. 0.25 mole of metallicsodium is added. Refluxing takes place for 6 hours. This is followed bythe dropwise addition of 0.2 mole of methyl iodide. The solution isfiltered, the filtrate dried on sodium sulphate and the amine distilled.TE_(b) =106° C. under 760 mmHg.

b) Preparation of the ligand

The procedure of example 1 is then adopted for preparing the ligand fromsaid amine.

The same operating procedure as in example 1 is then used for preparingthe technetium complex starting with said ligand. The characteristics ofthis complex are given in table 1.

EXAMPLE 8

The same operating procedure as in example 1 is followed for preparingthe technetium complex according to table 1 fromR,S-1-(methoxymethyl)-propyl amine prepared in the following way.

0.2 mole of (R,S)-2-amino-1-butanol (Aldrich) is prepared in 200 ml ofanhydrous ether under a nitrogen atmosphere, followed by the addition of0.25 mole of metallic sodium. Refluxing takes place for 6 hours,followed by the dropwise addition of 0.2 mole of methyl iodide. Thesolution is filtered, the filtrate dried on sodium sulphate and theamine is distilled, TE_(b) =102° C. under 760 nm Hg.

The characteristics of the complex obtained are given in table 1.

EXAMPLE 9

The same operating procedure as in the preceding examples is followedfor preparing the technetium complex according to table 1, using2-methoxyisobutyl amine prepared in the following way.

0.3 mole of 2-2-dimethyl aziridine is dissolved in 80 ml of methanolcontaining 0.35 mole of methanol trifluoroborane complex. Reaction isallowed to take place for 7 days at ambient temperature and 0.45 mole ofsodium methylate is added. The solution is filtered and distilled. Thetwo amines obtained are separated:

2-methoxyisobutyl amine, TE_(b) =126° C. under 760 mm Hg,

2-methoxy tert-butyl amine, TE_(b) =103° C. under 760 mm Hg

The characteristics of the complex obtained are given in table 1.

EXAMPLE 10

The operating procedure of example 1 is followed for preparing thetechnetium complex according to table 1 from the 2-methoxy tert-butylamine isolated in the preceding example.

The characteristics of the complex obtained are given in table 1.

EXAMPLES 11 AND 12

The technetium complexes according to table 1 are prepared, followingthe operating procedure of example 1, but starting withtetrahydro-furfuryl amine, which is treated by bromomethane in example11 and by bromoethane in example 12.

The characteristics of the complexes obtained are given in table 1.

EXAMPLE 13

The complex mentioned in table 1 is prepared by following the sameoperating procedure as in example 1, starting with N-ethyl.N-2-(2-methoxyethoxy)-ethyl amine prepared in the following way.

Dropwise addition takes place of 0.2 mole of1-bromo-2-(2-methoxyethoxy)-ethane (Aldrich) to an aqueous ethyl aminesolution. Refluxing takes place for 6 hours. The solution is filteredand is extracted with ether. The organic phase is distilled.

The characteristics of the complex obtained are given in table 1.

EXAMPLE 14

The complex according to table 1 is prepared by following the sameoperating procedure as in example 1, starting with the ligand sodium-N,N-bis(2,2-dimethoxyethyl)-dithiocarbamate, which is prepared fromN,N-bis(2 2-dimethoxyethyl)-amine obtained in the following way.

0.2 mole of dimethyl acetal aminoacetaldehyde (Aldrich) is dissolved in100 ml of water containing 0.3 mole of NaOH. Dropwise addition takesplace of 0.2 mole of dimethyl acetal bromoacetaldehyde (Aldrich). Thesolution is refluxed for one night. The aqueous phase is extracted with200 ml of diethyl ether. The organic phase is washed three times with 20ml of 1N NaOH in water in order to eliminate the primary amine which hasnot reacted. The organic phase is dried on sodium sulphate and thesecondary amine is distilled:

E=70° C. under 2 mm Hg.

NNIR analysis is deuterium DMSO of the ligand obtained ##STR15## givesthe following results: CH₃ O: singlet 3.4 ppm

CH: triplet 4.9 ppm

CH₂ : doublet 4.1 ppm

The characteristics of the complex obtained are given in table 1.

EXAMPLES 15 TO 24

The operating procedure of the preceding examples is followed forpreparing the complexes indicated in table 1, starting with the aminesand halides corresponding to the ligands of the complex.

The characteristics of the complexes obtained are given in table 1.

EXAMPLE 25

The biological properties of the complexes obtained in examples 1 to 24are evaluated by determining the cardiac retention in baboons weighingbetween 9 and 12 kg.

To this end, injection takes place of 0.5 ml of solution of the finalcomplex corresponding to an activity of 74 MBQ. The animal isanaesthetised by a ketamine/valium mixture and placed under a gammacamera. The retention of the radioactivity by the heart and thesurrounding organs (lungs, liver) is determined by a dynamic acquisitionfor 60 minutes following the injection. Determination takes place ofareas of interest for each organ and the retention values arecalculated, being expressed in counts per minute per pixel (surfaceunit) and per mCi (cpm.pix⁻¹ mCi⁻¹). These values are corrected by theradioactive decay of the radioelement. Blood samples are taken duringthe examination and their activity counted, which makes it possible tocalculate the radioactivity percentage present in the total blood(circulating activity).

The cardiac retention values, the heart/lungs and heart/liver ratiosgiving an indication of the scintigraphic contrast and the bloodactivity values obtained with the complexes of examples 1 to 24 aregiven in the following table 2.

This table gives for comparison purposes the results obtained under thesame conditions with the cardiac tracer MIBI marketed by Dupont and withthe prior art complies ^(99m) TcN-NOET, which is nitride-bis[N-ethoxy,N-ethyl-dithiocarbamate]^(99m) Tc(V) and which complies withformula (I), in which L¹ and L² are: ##STR16##

The results of table 2 demonstrate that most of the complexes have acardiac retention superior to that of MIBI and equivalent to that of TcNNOET.

However, the cardiac activity decreases in time, which leads to a dropin the heart/lung and heart/liver scintigraphic ratios.

The blood clearance is rapid for most of the tested complexes.

The ideal period for cardiac imaging with this type of complex isconsequently between 5 and 30 minutes after the injection.

The rapid elimination of the myocardium can permit a second injection 1hour after the first, because the residual hepatic activity is no longerdisturbing, because it is concentrated in the gall bladder with thistype of tracer.

Thus, the scintigraphic images show that one hour after the injection,the residual hepatic activity is concentrated in the gall bladder,except for the complex of example 24.

Conversely, the scintigraphic images taken of the baboon with compoundsof examples 11 and 17 of WO-A-90/06137 revealed that the residualhepatic activity was maintained throughout the liver.

It is also pointed out that the complexes which are of greatest interestare those of examples 1, 2, 3, 7, 12, 14, 15 and 18, the best beingthose of examples 1, 2, 3, 14, 15 and 18.

                                      TABLE 1                                     __________________________________________________________________________    EXAMPLE                                                                             COMPLEX          L.sup.1 = L.sup.2                                                                             Rf PRC                                 __________________________________________________________________________    1     nitrido-bis[N-ethyl, N-(RS-2-methoxy  isopropyl)dithiocarbamato].sup          .99m TC(V)                                                                                      ##STR17##      0.52                                                                             ≧96%                         2     nitrido-bis[N-ethyl, N-(R-2-methoxy  isopropyl)dithiocarbamato].sup.          99m Tc(V)                                                                                       ##STR18##      0.52                                                                             ≧97%                         3     nitrido-bis[N-ethyl, N-(S-2-methoxy  isopropyl)dithiocarbamato].sup.          99m Tc(V)                                                                                       ##STR19##      0.52                                                                             ≧95%                         4     nitrido-bis[N-methyl, N-(RS-2-methoxy  isopropyl)dithiocarbamato].su          p.99m Tc(V)                                                                                     ##STR20##      0.61                                                                             ≧96%                         __________________________________________________________________________

                                      TABLE 1(a)                                  __________________________________________________________________________    EXAMPLE                                                                             COMPLEX            L.sup.1 = L.sup.2                                                                             Rf PRC                               __________________________________________________________________________    5     nitrido-bis[N-propyl, N-(R,S-2-methoxy  isopropyl)dithiocarbamato].s          up.99m Tc(V)                                                                                      ##STR21##      0.39                                                                             ≧97%                       6     nitrido-bis[N-isopropyl, N-(R,S-2-methoxy  isopropyl)dithiocarbamato          ].sup.99m Tc(V)                                                                                   ##STR22##      0.35                                                                             ≧92%                       7     nitrido-bis[N-ethyl, N-(R,S-2-methoxy  propyl)dithiocarbamato].sup.9          9m Tc(V)                                                                                          ##STR23##      0.45                                                                             ≧98%                       8     nitrido-bis[N-ethyl, N-(R,S-1-methoxy  methyl) propyl                         dithiocarbamato].sup.99m Tc(V)                                                                    ##STR24##      0.46                                                                             ≧98%                       __________________________________________________________________________

                                      TABLE 1(b)                                  __________________________________________________________________________    EXAMPLE                                                                             COMPLEX              L.sup.1 = L.sup.2                                                                            Rf PRC                              __________________________________________________________________________    9     nitrido-bis[N-ethyl,N-(2-methoxy isobutyl)  dithiocarbamato].sup.99m           Tc(V)                                                                                              ##STR25##     0.43                                                                             ≧92%                      10    nitrido-bis[N-ethyl,N-(2-methoxy tertbutyl)  dithiocarbamato].sup.99          m Tc(V)                                                                                             ##STR26##     0.50                                                                             ≧95%                      11    nitrido-bis[N-methyl,N(R,S,-1-tetrahydrofurfuryl)                             dithiocarbamato].sup.99m Tc(V)                                                                      ##STR27##     0.70                                                                             ≧95%                      __________________________________________________________________________

                                      TABLE 1(c)                                  __________________________________________________________________________    EXAMPLE                                                                              COMPLEX               L.sup.1 = L.sup.2        Rf  PRC                 __________________________________________________________________________    12     nitrido-bis[N-ethyl, N(R,S 1-tetrahydrofurfuryl)                              dithiocarbamato].sup.99m Tc(v)                                                                       ##STR28##               0.61                                                                              ≧97%         13     nitrido-bis[N-ethyl, N-2(2-methoxy ethoxy)ethyl)                              dithiocarbamato].sup.99m Tc(V)                                                                       ##STR29##               0.71                                                                              ≧98%         14     nitrido-bis[N-N-bis(2,2-dimethoxy ethyl)  dithiocarbamato].sup.99m            Tc(V)                                                                                                ##STR30##               0.45                                                                              ≧96%         __________________________________________________________________________

                                      TABLE 1(d)                                  __________________________________________________________________________    EXAMPLE                                                                             COMPLEX            L.sup.1 = L.sup.2    Rf PRC                          __________________________________________________________________________    15    nitrido-bis[N-(2,2-dimethoxyethyl)N-(3,3-  diemthoxypropyl)dithiocar          bamato].sup.99m Tc(V)                                                                             ##STR31##           0.45                                                                             ≧97%                  16    nitrido-bis[N-(2,2-dimethoxyethyl)N-(2,2-  dimethoxypropyl)dithiocar          bamato].sup.99m Tc(V)                                                                             ##STR32##           0.40                                                                             ≧94%                  17    nitrido-bis[N-(2,2-dimethoxyethyl)N-(2,2-  diethoxyethyl)dithiocarba          mato].sup.99m Tc(V)                                                                               ##STR33##           0.33                                                                             ≧95%                  __________________________________________________________________________

                                      TABLE 1(e)                                  __________________________________________________________________________    EXAMPLE                                                                             COMPLEX                L.sup.1 = L.sup.2                                                                             Rf PRC                           __________________________________________________________________________    18    nitrido-bis[N-(2,2-dimethoxy ethyl)N-  (ethyl)dithiocarbamato].sup.9          9m Tc(V)                                                                                              ##STR34##      0.47                                                                             ≧96%                   19    nitrido-bis[N-(2,2-dimethoxy ethyl)N-  (isopropyl)dithiocarbamato].s          up.99m Tc(V)                                                                                          ##STR35##      0.35                                                                             ≧95%                   20    nitrido-bis[N-(2,2-dimethoxy ethyl)N-  (R,S-2-methoxy                         isopropyl)dithiocarbamato].sup.99m Tc(V)                                                              ##STR36##      0.47                                                                             ≧92%                   __________________________________________________________________________

                                      TABLE 1(f)                                  __________________________________________________________________________    EXAMPLE                                                                             COMPLEX                   L.sup.1 = L.sup.2                                                                              Rf PRC                       __________________________________________________________________________    21    nitrido-bis[N-N-bis(2,2-diethoxyethyl)  dithiocarbamato].sup.99m              Tc(V)                                                                                                    ##STR37##       0.13                                                                             ≧98%               22    nitrido-bis[N-(2,2-diethoxyethyl, N(2,2-diethylene acetal)                    ethyl)dithiocarbamato].sup.99m Tc(V)                                                                     ##STR38##       0.37                                                                             ≧95%               23    nitrido-bis[N-N-bis(2,2-diethylene acetal  ethyl)dithiocarbamato].su          p.99m Tc(V)                                                                                              ##STR39##       0.55                                                                             ≧95%               24    nitrido-bis[8-aza-1,4-dioxaspiro(4,5)  decane dithiocarbamato].sup.9          9m Tc(V)                                                                                                 ##STR40##       0.52                                                                             ≧93%               __________________________________________________________________________

                                      TABLE 2                                     __________________________________________________________________________           .sup.99m Tc Complex                                                           Cardiac retention                  Blood activity                      Time after                                                                           cpm · pix.sup.-1 mCi.sup.-1                                                    Heart/lungs                                                                             Heart/liver    (% injected dose)                   injection (min)                                                                      5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5  10 15 30 60 5  10                                                                              15                                                                              30                                                                              60                         __________________________________________________________________________    .sup.99m Tc MIBI                                                                     21                                                                              21                                                                              21                                                                              18                                                                              17                                                                              3.1                                                                             3.1                                                                             3.1                                                                             2.7                                                                             3 0.55                                                                             0.56                                                                             0.55                                                                             0.66                                                                             0.75                                                                             15 1.7                                                                             0.8                                                                             0.7                                                                             0.8                        .sup.99m TcN NOET                                                                    39                                                                              37                                                                              35                                                                              35                                                                              34                                                                              1.1                                                                             1.3                                                                             1.4                                                                             1.8                                                                             2.3                                                                             1.4                                                                              1.2                                                                              1  0.9                                                                              0.8                                                                              2.4                                                                              2 1.7  1.6                                                                      1.9                            EXAMPLE 1                                                                            44                                                                              42                                                                              40                                                                              33                                                                              24                                                                              3.9                                                                             4.3                                                                             4.5                                                                             3.9                                                                             3.2                                                                             1  0.8                                                                              0.6                                                                              0.3                                                                              0.3                                                                              8  --                                                                              3    2                                                                        1.5                            EXAMPLE 2                                                                            31                                                                              27                                                                              26                                                                              24                                                                              22                                                                              2.7                                                                             2.9                                                                             2.7                                                                             2.7                                                                             2.5                                                                             0.8                                                                              0.6                                                                              0.6                                                                              0.5                                                                              0.4                                                                              -- 5.2                                                                             3.2  2.9                                                                      --                             EXAMPLE 3                                                                            30                                                                              21                                                                              17                                                                              12                                                                              11                                                                              2.6                                                                             2.2                                                                             1.9                                                                             1.4                                                                             1.4                                                                             0.5                                                                              0.3                                                                              0.2                                                                              0.2                                                                              0.1                                                                              4.8                                                                              --                                                                              1.9  1.3                                                                      1.1                            EXAMPLE 4                                                                            35                                                                              22                                                                              18                                                                              14                                                                              12                                                                              5 3.1                                                                             2.6                                                                             2.2                                                                             2 0.6                                                                              0.3                                                                              0.3                                                                              0.2                                                                              0.2                                                                              -- 4.6                                                                             4.6  2.4                                                                      1.8                            EXAMPLE 5                                                                            45                                                                              38                                                                              35                                                                              21                                                                              12                                                                              3.7                                                                             3.6                                                                             3.6                                                                             2.6                                                                             1.8                                                                             0.6                                                                              0.5                                                                              0.4                                                                              0.2                                                                              0.1                                                                              6.7                                                                              3.9                                                                             --   3.6                       __________________________________________________________________________

                                      TABLE 2(a)                                  __________________________________________________________________________           .sup.99m Tc Complex                                                           Cardiac retention             Blood activity                           Time after                                                                           cpm · pix.sup.-1 mCi.sup.-1                                                    Heart/lungs                                                                             Heart/liver                                                                             (% injected dose)                        injection (min)                                                                      5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5  10                                                                              15                                                                              30                                                                              60                              __________________________________________________________________________    EXAMPLE 6                                                                            32                                                                              27                                                                              25                                                                              18                                                                              14                                                                              2.9                                                                             2.9                                                                             2.7                                                                             2.1                                                                             1.8                                                                             0.4                                                                             0.3                                                                             0.2                                                                             0.2                                                                             0.1                                                                             11 6.5                                                                             5.1                                                                             3.7                               EXAMPLE 7                                                                            51                                                                              41                                                                              38                                                                              28                                                                              22                                                                              4.1                                                                             4.3                                                                             4.2                                                                             3.4                                                                             2.9                                                                             0.8                                                                             0.6                                                                             0.5                                                                             0.3                                                                             0.2                                                                             4.4                                                                              3.5                                                                             2.8  2                                                                        1.7                                 EXAMPLE 8                                                                            36                                                                              32                                                                              24                                                                              16                                                                              11                                                                              3.3                                                                             3.5                                                                             3.1                                                                             2.4                                                                             1.8                                                                             0.6                                                                             0.5                                                                             0.3                                                                             0.2                                                                             0.2                                                                             8.5  5    2.8                                                                      2.1                                 EXAMPLE 9                                                                            26                                                                              21                                                                              16                                                                              13                                                                              12                                                                              3 2.9                                                                             2.2                                                                             2 1.7                                                                             0.4                                                                             0.3                                                                             0.2                                                                             0.2                                                                             0.2                                                                             5.9                                                                              --                                                                              3.6  2.4                                                                      1.5                                 EXAMPLE 10                                                                           31                                                                              25                                                                              23                                                                              19                                                                              14                                                                              3.2                                                                             3.1                                                                             3 2.8                                                                             2.2                                                                             0.5                                                                             0.4                                                                             0.3                                                                             0.2                                                                             0.2                                                                             9.4                                                                              --                                                                              7.1  4.9                                                                      --                                  EXAMPLE 11                                                                           41                                                                              26                                                                              21                                                                              14                                                                              11                                                                              4.5                                                                             3.2                                                                             2.7                                                                             1.9                                                                             1.7                                                                             0.7                                                                             0.4                                                                             0.3                                                                             0.2                                                                             0.1                                                                             -- 5.3                                   EXAMPLE 12                                                                           35                                                                              28                                                                              25                                                                              16                                                                              11                                                                              3.1                                                                             2.9                                                                             2.7                                                                             1.9                                                                             1.7                                                                             0.6                                                                             0.4                                                                             0.4                                                                             0.2                                                                             0.1                                                                             4.3  2.5  1.5                                                                      1.3                                 __________________________________________________________________________

                                      TABLE 2(b)                                  __________________________________________________________________________           .sup.99m Tc Complex                                                           Cardiac retention             Blood activity                           Temps apres                                                                          cpm · pix.sup.-1 mCi.sup.-1                                                    Heart/lungs                                                                             Heart/liver                                                                             (% injected dose)                        injection (min)                                                                      5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5  10                                                                              15                                                                              30                                                                              60                              __________________________________________________________________________    EXAMPLE 13                                                                           37                                                                              35                                                                              34                                                                              22                                                                              14                                                                              2.9                                                                             3.3                                                                             3.3                                                                             2.5                                                                             1.9                                                                             0.6                                                                             0.5                                                                             0.4                                                                             0.2                                                                             0.1                                                                             4.5                                                                              --                                                                              2.4                                                                             2.1                                                                             1.6                             EXAMPLE 14                                                                           46                                                                              41                                                                              34                                                                              20                                                                              11                                                                              4.9                                                                             5 4.2                                                                             2.9                                                                             2 0.9                                                                             0.6                                                                             0.5                                                                             0.3                                                                             0.2                                                                             6.8                                                                              --                                                                              5    4.3                                                                      2.7                                 EXAMPLE 15                                                                           49                                                                              44                                                                              39                                                                              25                                                                              15                                                                              4.1                                                                             4.4                                                                             4.4                                                                             3.2                                                                             2.2                                                                             0.8                                                                             0.6                                                                             0.5                                                                             0.3                                                                             0.2                                                                             12 5 4.5                                 EXAMPLE 16                                                                           44                                                                              37                                                                              33                                                                              21                                                                              12                                                                              3.3                                                                             3.3                                                                             3 2.2                                                                             1.6                                                                             0.8                                                                             0.6                                                                             0.                                                                              0.2                                                                             0.1                                                                             3.9                                                                              4.2                                                                             4.3  4                                                                        2.7                                 EXAMPLE 17                                                                           29                                                                              27                                                                              26                                                                              23                                                                              19                                                                              3 3.1                                                                             3.2                                                                             3.1                                                                             2.7                                                                             0.5                                                                             0.4                                                                             0.4                                                                             0.3                                                                             0.3  4.5                                                                             2.4  2.1                            EXAMPLE 18                                                                           40                                                                              34                                                                              28                                                                              19                                                                              13                                                                              3.7                                                                             3.5                                                                             3 2.1                                                                             1.4                                                                             0.6                                                                             0.5                                                                             0.4                                                                             0.2                                                                             0.1                                                                             8.6                                                                              4.2                                                                             3.8  2.5                            EXAMPLE 19                                                                           31                                                                              28                                                                              27                                                                              21                                                                              15                                                                              2.7                                                                             2.8                                                                             2.8                                                                             2.5                                                                             1.9                                                                             0.4                                                                             0.4                                                                             0.3                                                                             0.3                                                                             0.2                                                                             7.6  5.2  5.6                                                                      4.5                                 __________________________________________________________________________

                                      TABLE 2(c)                                  __________________________________________________________________________           .sup.99m Tc Complex                                                           Cardiac retention             Blood activity                           Time after                                                                           cpm · pix.sup.-1 mCi.sup.-1                                                    Heart/lungs                                                                             Heart/liver                                                                             (% injected dose)                        injection (min)                                                                      5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5 10                                                                              15                                                                              30                                                                              60                                                                              5  10 15                                                                              30                                                                              60                             __________________________________________________________________________    EXAMPLE 20                                                                           42                                                                              35                                                                              2.9                                                                             16                                                                              13                                                                              3.2                                                                             3 2.7                                                                             1.8                                                                             1.5                                                                             0.9                                                                             0.6                                                                             0.4                                                                             0.2                                                                             0.1                                                                             10.1                                                                             8.9                                                                              8.7                                                                             8.3                                                                             7.6                            EXAMPLE 21                                                                           26                                                                              18                                                                              15                                                                              13                                                                               9                                                                              2 1.7                                                                             1.6                                                                             1.4                                                                             1.3                                                                             0.5                                                                             0.3                                                                             0.3                                                                             0.2                                                                             0.2                                                                             23.2                                                                             12.5    4.3                           EXAMPLE 22                                                                           36                                                                              25                                                                              21                                                                              15                                                                              10                                                                              3.3                                                                             3 2.6                                                                             2.1                                                                             1.6                                                                             0.6                                                                             0.4                                                                             0.3                                                                             0.2                                                                             0.2                                                                             5.1                                                                              3.9     3                             EXAMPLE 23                                                                           36                                                                              24                                                                              19                                                                              13                                                                               9                                                                              3.6                                                                             2.6                                                                             2 1.5                                                                             1.2                                                                             0.9                                                                             0.5                                                                             0.3                                                                             0.2                                                                             0.3                                                                             9.2                                                                              3.5                                                                              2.8                                EXAMPLE 24                                                                           23                                                                              16                                                                              14                                                                              13                                                                              12                                                                              2.4                                                                             1.7                                                                             1.5                                                                             1.4                                                                             1.4                                                                             0.3                                                                             0.3                                                                             0.2                                                                             0.2                                                                             0.2                                                                             4.6                                                                              -- 3.3  2.5                                                                      --                                 __________________________________________________________________________

We claim:
 1. A radiopharmaceutical product, comprising a complex of atransition metal of the formula:

    (M.tbd.N)L.sup.1 L.sup.2                                   (I)

in which M is a transition metal, and L¹ and L², which can be the sameor different, comply with the formula: ##STR41## in which R and R',which are the same or different, represent: an alkyl group, a group offormula: ##STR42## in which: R¹ is an alkyl group, R² is an alkyl groupor an alkoxy group, or R¹ and R² form together the group --CH₂ CH₂ O--,R³ is a hydrogen atom or an alkyl group and n is equal to 0, 1, 2 or 3,a group of formula: ##STR43## in which R¹ and R³ are as definedhereinbefore and R⁴ is an alkyl group, the group of formula: ##STR44## agroup of formula:

    R.sup.1 O(CH.sub.2 CH.sub.2 O).sub.p CH.sub.2 CH.sub.2 --  (VI)

in which R¹ is as defined hereinbefore and p is equal to 1 or 2, or inwhich R and R' together with the nitrogen atom to which they are linked,form the group of formula: ##STR45## in which R¹ and R⁵ are identical ordifferent alkyl groups, or in which R¹ and R⁵ form together --CH₂ --CH₂--, provided that both R and R' do not represent an alkyl group.
 2. Aradiopharmaceutical product according to claim 1, wherein M representsan isotope of technetium or rhenium.
 3. A radiopharmaceutical productaccording to claim 2, wherein the isotope of technetium is Tc-99m.
 4. Aradiopharmaceutical product according to claim 2, wherein the isotope ofrhenium is Re-186 or Re-188.
 5. A radiopharmaceutical product accordingto claim 1, wherein L¹ and L² are identical.
 6. A radiopharmaceuticalproduct according to claim 1, wherein at least one of the L¹ and L²complies with the formula (II) in which:R and/or R' represent a group offormula: ##STR46## in which R¹ represents an alkyl group, R² representsan alkoxy group, R³ represents a hydrogen atom or an alkyl group, and nis equal to 0, 1, 2 or
 3. 7. A radiopharmaceutical product according toclaim 1, wherein at least one of the L1 and L2 complies with the formula(II) in which:R and/or R' represent a group of formula: ##STR47## inwhich R¹, R² and R³ are identical or different alkyl groups.
 8. Aradiopharmaceutical product according to claim 1, wherein the complex ischosen from within the group consistingof:nitrido-bis[N-ethyl-N(R,S-methoxypropyl)dithiocarbamato]^(99m) Tc(V),nitrido-bis[N-ethyl-N(2-methoxyisobutyl)dithiocarbamato]^(99m) Tc(V),nitrido-bis[N-,N-bis-2,2-dimethoxyethyl)dithiocarbamato]^(99m) Tc(V),nitrido-bis[N-(2,2-dimethoxyethyl), N-(3,3-dimethoxypropyl)dithiocarbamato]^(99m) Tc(V),nitrido-bis[N-(2,2-dimethoxyethyl), N-(2,2-dimethoxypropyl)dithiocarbamato]^(99m) Tc(V), nitrido-bis[N-(2,2-dimethoxyethyl),N-(2,2-diethoxyethyl) dithiocarbamato]^(99m) Tc(V),nitrido-bis-[N-(2,2-dimethoxyethyl), N-ethyl dithiocarbamato]^(99m)Tc(V), nitrido-bis [N-(2,2-dimethoxyethyl), N-isopropyldithiocarbamato]^(99m) Tc(V), nitrido-bis[N,N-bis(2,2-diethoxyethyl),dithiocarbamato]^(99m) Tc(V), nitrido-bis[N-(2,2-diethoxyethyl),N(2,2(diethyleneacetal)ethyl) dithiocarbamato]^(99m) Tc(V),nitrido-bis-[N,N-bis(2,2(diethyleneacetal)ethyl) dithiocarbamato]^(99m)Tc(V).
 9. A radiopharmaceutical product according to any claim 1,wherein at least one of the L1 and L2 complies with formula (II) inwhich:R and/or R' comply with the formula (IV): ##STR48## in which R¹represents an alkyl group, R³ represents a hydrogen atom and R⁴represents an alkyl group.
 10. A radiopharmaceutical product accordingto claim 9, wherein the complex is chosen in the group consistingof:nitrido-bis[N-ethyl, N-(R-S-2 methoxyisopropyl)dithiocarbamato]^(99m) Tc(V), nitrido-bis[(N-ethyl,N-(R-2-methoxyisopropyl) dithiocarbamato]^(99m) Tc(V),nitrido-bis[(N-ethyl, N(S-2-methoxyisopropyl) dithiocarbamato]^(99m)Tc(V), nitrido-bis[(N-methyl, N(R,S)-2-methoxyisopropyl)dithiocarbamato]^(99m) Tc(V), nitrido-bis[(N-propyl,N-(R,S)2-methoxyisopropyl) dithiocarbamato]^(99m) Tc(V),nitrido-bis[N-isopropyl, N(R,S)-2-methoxyisopropyl)dithiocarbamato]^(99m) Tc(V), nitrido-bis[(N-ethyl,N(R,S)-1-methoxymethyl)propyl) dithiocarbamato]^(99m) Tc(V),nitrido-bis[N-ethyl, N-(2-methoxy tert-butyl) dithiocarbamato]^(99m)Tc(V), nitrido-bis[N-(2,2-dimethoxyethyl), N(R,S)2-methoxyisopropyl)dithiocarbamato]^(99m) Tc(V).
 11. A radiopharmaceutical productaccording to claim 1, wherein at least one of the L¹ and L² complieswith formula (II) in which:R and/or R¹ represent the group of formula:##STR49##
 12. A radiopharmaceutical product according to claim 11,wherein the complex is chosen from among: nitrido-bis[(N-methyl, N-(R,S)1-tertrahydrofurfuryl) dithiocarbamato]^(99m) Tc(V),andnitrido-bis[(N-ethyl N-(R,S) 1-tetrahydrofurfuryl)dithiocarbamato]^(99m) Tc(V).
 13. A radiopharmaceutical productaccording to claim 1, wherein the complex is nitrido-bis[(N-ethyl,N-2(2-methoxyethoxy) ethyl) dithiocarbamato]^(99m) Tc(V) ornitrido-bis[8-aza-1,4-dioxaspiro (4,5)-decane dithiocarbamato]^(99m)Tc(V).
 14. A process for the preparation of a radiopharmaceuticalproduct according to claim 1, comprising reacting in solution an oxygencompound of the transition metal M, with 1) a nitrogen ligandconstituted either by a pharmaceutically acceptable metal or ammoniumnitride, or by a nitrogen compound having a N--N unit, in which the Nsare connected to hydrogen atoms and/or monovalent organic groups via acarbon atom or a S atom, or in which one of the Ns is connected to thecarbon atom of a divalent organic group via a double bond and the otherN is connected to hydrogen atoms and/or monovalent organic groups via acarbon atom;2) a reducing agent constituted either by a pharmaceuticallyacceptable metal or ammonium dithionite, or by tin II present in ionicform in the solution; and 3) a compound complying with the formula:##STR50## in which R and R' have the meanings given hereinbefore, R⁶ isan alkali metal, H⁺ or NH⁴⁺ ion, and x is equal to 0 or an integer from1 to
 5. 15. The process according to claim 14, wherein the nitrogenligand is succinyl dihydrazide and the reducing agent stannous chloridedihydrate.
 16. A kit for the preparation of the radiopharmaceuticalproduct according to claim 1, comprising:a first bottle containing a tinsalt and a complexing agent able to keep the tin in ionic form, a secondbottle containing a nitrogen ligand and a third bottle containing acompound complying with the formula: ##STR51## in which R and R' havethe meanings given in claim 1, R⁶ is an alkali metal, H⁺ or NH⁴⁺ ion,and x is equal to 0 or an integer from 1 to
 5. 17. A kit for thepreparation of the radiopharmaceutical product according to claim 1,comprising:a first bottle containing a tin salt, a nitrogen ligand and acomplexing agent able to keep the tin in ionic form and a second bottlecontaining a compound of formula: ##STR52## in which R and R' have themeanings given in claim 1, R⁶ is an alkali metal, H⁺ or NH⁴⁺ ion, and xis equal to 0 or an integer from 1 to
 5. 18. The kit according to claim16, wherein the compound of formula (VIII) is selected from the groupconsisting of:sodium-(N-ethyl,N-(R,S)-2-methoxyisopropyl)-dithiocarbamate, sodium-(N-ethyl,N(R)-2-methoxyisopropyl)-dithiocarbamate, sodium-(N-ethyl,N-(S)-2-methoxyisopropyl)-dithiocarbamate,sodium-[N,N-bis(2,2-dimethoxyethyl)]-dithiocarbamate,sodium-[N-(2,2-dimethoxyethyl),N-(3,3-dimethoxypropyl)]-dithiocarbamate,sodium-[N](2,2-dimethoxyethyl), N-ethyl)]-dithiocarbamate.
 19. The kitaccording to claim 16, characterized in that the tin salt is stannouschloride, the complexing agent is1,2-diaminopropane-N,N,N',N'-tetraacetic acid or a salt thereof and thenitrogen ligand is succinyl dihydrazide.
 20. A radiopharmaceuticalproduct according to any one of the claims 1 to 13 for scintigraphy ofthe myocardium.
 21. The kit according to claim 17, wherein the compoundof formula (VIII) is selected from the group consistingofsodium-(N-ethyl, N-(R,S)-2-methoxyisopropyl)-dithiocarbamate,sodium-(N-ethyl, N-(R)-2-methoxyisopropyl)-dithiocarbamate,sodium-(N-ethyl, N-(S)-2-methoxyisopropyl)-dithiocarbamate, sodium-[N,N-bis(2,2-dimethoxyethyl)]-dithiocarbamate,sodium-[N-(2,2-dimethoxyethyl),N-(3,3-dimethoxypropyl)]-dithiocarbamate, andsodium-[N-(2,2-dimethoxyethyl), N-ethyl)]-dithiocarbamate.
 22. The kitaccording to claim 17, wherein the tin salt is stannous chloride, thecomplexing agent is 1,2-diaminopropane-N,N,N',N'-tetraacetic acid or asalt thereof, and the nitrogen is succinyl dihydrazide.